Naive animals, always starting from the same location in the maze (the “south” arm), were trained to selleck chemical find

a fixed target site (in the “east” arm) (Training I in Figure 6A). In order to facilitate developing habit-based navigation, the north and the west arms were both closed. It has been shown that under this paradigm, normal mice would learn to search the target using spatial reference memory after moderate training but would switch to habitual navigation after extensive training ( Packard and McGaugh, 1996). Probe trials, during which the start location switched from the “south” arm to the “north” arm, were given at different time points to allow dissociation of the spatial and habitual strategies. Thus, mice using the “habit strategy” were predicted to turn right (into the “west” arm), whereas the “spatial” mice, guided by distal spatial cues, were predicted to go to the “east” arm, where the target resided during training. All mice were trained in ten trials per day for 5 consecutive

days before the first probe trial on day 6 (Probe 1 in Figure 6A). During this probe trial the DA-NR1-KO group and control mice showed Selleckchem SCH 900776 similar preferences (χ2 [3, n = 43] = 0.346; p = 0.951) for the “spatial” strategy, opting to turn left toward the “east” arm (Figure 6B), suggesting that they had similarly acquired the spatial memory and that they shared comparable

motivation. All mice were then trained for 10 additional days before the second probe trial (Probe 2 in Figure 6A) on day 17. During this probe trial no significant differences were found among the three control groups (χ2 [2, n = 29] = 0.499; p = 0.779). As a group, control mice opted to “turn right” (and into the “west” arm) significantly more on day 17 than on day 6 (χ2 [1, n = 29] = 22.587; p = 0.00000201), indicating a learned “habit”-based searching strategy. In contrast, less than 10% of the DA-NR1-KO mice (compared with 80% of control mice) (mutants versus controls: χ2 = 7.244; p = 0.007) opted to turn “right” on day 17 (Figure 6B), suggesting that they failed to learn the “habit”-based strategies and, instead, kept using the “spatial” strategy. To confirm that the deficits in the plus maze tasks were indeed Cell press from habit learning, right after the second probe trial, mice were further challenged in a “relearn after 90° rotation” procedure (Training II, Figure 6A), three trials a day for 2 days within the exact same maze and surrounding cues. During the training, both the west and south arms were blocked. The start box was placed in the “east” arm, and the food rewards were in the “north” arm. Mice were tested in a rotation test on day 19, and accuracies to locate the food were scored. Mice started from the “east” arm with all arms open during the test (Figure 6A).